Genome-Wide Analysis of Uveal Melanoma Metastasis-Associated LncRNAs and Their Functional Network

摘要

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Up to 50% of primary UM cases will develop distant metastasis, but no effective therapies are currently available. The present study aimed to characterize the expression profile of the long noncoding RNAs (lncRNAs) and screen the potential metastasis-associated lncRNAs in UM. A genome-wide analysis of the transcriptome was performed on 11 primary UM tissues (6 metastasized and 5 nonmetastasized) through RNA sequencing. A total of 40,878 lncRNAs were detected in UM, 4,983 of which were novel candidates. We identified 329 differentially expressed lncRNAs (DELs) and 802 differentially expressed mRNAs (DEMs) by comparing the transcriptome profile between metastasized and nonmetastasized UM group. The DEL–DEM coexpression network revealed that the RP11-551L14.4, TCONS_00004101, and TCONS_00004845 DELs had the highest connectivity with the DEMs, coexpressed with 225, 28, and 10 DEMs, respectively, whereas the SPOCD1 , PEA15 , and SLC44A3 DEMs were most closely connected with the DELs, and were coexpressed with 89, 27, and 22 DELs, respectively. Moreover, 17 and 743 DEMs were targeted by the DELs through cis- or trans-action, respectively. These targeted DEMs were significantly enriched in D-Arginine and D-ornithine metabolism and glycerolipid metabolism of Kyoto Encyclopedia of Genes and Genomes pathways, and enriched in bradykinin receptor activity and haptoglobin binding of gene ontology biological processes. Quantitative real-time PCR confirmed the sequencing data. These findings have provided new insights into the molecular mechanism of UM metastasis and paved the way for further investigations regarding lncRNA in UM.